"Raising Arizona" as a metaphor for a disappearing extended Orange Book patent

In the movie "Raising Arizona" a female ex-cop and her ex-con boyfriend conspire to kidnap a baby from a couple that recently had quintuplets. Their rationale was that, with so many babies in the house to take care of, the parents wouldn't notice that one was missing!

While the plot of "Raising Arizona" was absurd, you might also think that an NDA holder would notice when one of its Orange Book-listed patents went missing, right? Well, maybe not if the product had six strengths, each with eight patents listed, and the patent disappeared from the listings of only one of those six strengths. That is exactly what appears to have happened to a Takeda drug called Oseni® (alogliptin benzoate/pioglitazone HCl).

Patent 6,329,404 was originally listed in the February 2013 supplement of the Orange Book along with sixteen other patents for all six strengths of OSENI following the drug's approval in January 2013. On June 15, 2016 the '404 patent received a five-year Patent Term Extension to June 19, 2021.

The FDA updated the expiration date of the '404 patent in Supplement 1 of the 2017 Orange Book, but only for five of OSENI's six strengths! The expiration date of the 12.5mg/45mg strength (Product No. 006) of OSENI was not updated from its original June 19, 2016 date. Since the FDA has an annual process of deleting expired patents from the Orange Book in the first supplement of a new year, Prod. No. 006's listing of the '404 patent with its original 2016 expiration date ended up getting deleted from the 2017 Orange Book. Poof!

How did I discover the disappearance of the ‘404 patent from Prod. No. 006’s patent listings?

For the sake of simplicity, my Orange Book Companion® (“OBC”) algorithms combine the patent and exclusivity information of a drug into a single table when that information is identical for multiple strengths of the drug (each strength with a unique Orange Book “Product Number”). A strength with even the slightest difference will be broken out into a separate table. So one day while scrolling through the OBC page of trademarks beginning with “O” I noticed two tables for Takeda’s OSENI. The first contained the patent and exclusivity information for Prod. Nos. 001-005. The second contained the patent and exclusivity information for Prod. No. 006 (12.5mg/45mg).

So what was the difference?

Unlike the disappearance of an exclusivity that I blogged about previously which involved a single digit difference, this one was easy to spot. The ‘404 patent was missing from the Prod. No. 006 listing! See for yourself.

To see if Takeda had left out the 12.5mg/45mg strength (Prod. No. 006), either deliberately or accidentally, I made a FOIA request for their 3542 forms. As a result I received two 3542 forms (dated January 19, 2017 and February 7, 2017) that Takeda had submitted to the FDA to update the '404 patent's expiration date as a result of the PTE. (The second form was possibly submitted to correct a typo in the email address of the Takeda contact person). Both of those 3542 forms listed all six strengths of OSENI. That makes it likely that the source of the ‘404 patent’s disappearance from the Prod. No. 006 patent listings was the FDA rather than Takeda.

This oversight by the FDA occurred over two years ago. If we go back to the “Raising Arizona” metaphor, with OSENI having six strengths each having a bunch of listed patents, I guess that no one at Takeda has ever noticed that one of their babies is missing!

So what should a company do to prevent such a disappearance?

Do not just submit 3542 forms to the FDA and hope for the best. The Orange Book Staff has a lot of work to do besides keeping the patent information up to date. If you have ever seen a printed Orange Book you would appreciate that the patent and exclusivity info is nothing but a little addendum in the back of a very thick book. There is a whole lot more info in the Orange Book than just the patent and exclusivity data.

So it is your responsibility as the NDA holder to carefully check your listings after to you make an Orange Book patent submission. You must always remember that each strength of a drug has its own individual portfolio of patent and exclusivity data. So just checking the listings for one strength (or even five out of six strengths as in the case of OSENI) is not good enough. You may even want to consider getting a subscription to the Orange Book Companion and let my algorithms do part of the work!


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